Dr. Cox is an infectious disease fellow at the Johns Hopkins University (JHU) and has spent the last two years working with her mentors, Drs Thomas, Ray, and Pardoll on the cellular and humoral immune responses to hepatitis C virus (HCV) infection. Through this award, Dr. Cox hopes to conduct basic science research on HCV immunology as a faculty member in the Division of Infectious Diseases. To elucidate the effects of HIV infection of CD4+ T cell on the immune response to chronic hepatitis C virus (HCV) infection, she plans to characterize the humoral and cellular immune responses to HCV in the same subjects before and after HIV infection. Her hypothesis is that HIV infection alters CD4+ T cell by destruction or dysregulation, an effect that in turn modifies B cell and CD8+ T cell activity. Through the sponsor's research, cells, plasma, and serum have been collected before and after HIV infection from individuals with chronic HCV. Humoral responses to each HCV protein at multiple time points before and after HIV infection will be assessed using an ELISA assay optimized for the measurement of end-point titers of IgM, IgG, and the four IgG subtypes specific for HCV CD8+ T cell responses will be measured at multiple time points before and after HIV infection using an Elispot assay for the detection of gamma interferon. Finally, the cytokine secretion profiles of CD4+ T cell will be assessed to determine if alterated cytokine production is correlated with any observed changes in B cell or T cell function. We anticipate that this study will provide insight into the impact of HIV infection on CD4+ T cell effector function, will increase understanding of HCV immune responses and control of HCV viremia, and will enhance future research aimed at elucidating the mechanisms of interaction between HIV and HCV that lead to differences in the pathogenesis and control of HCV seen with HIV co-infection. Since no direct patient contact is anticipated, Dr. Cox plans to conduct these studies through a K08 award. Dr. Cox will attend immunology, virology, and infectious disease seminars. This, along with excellent mentorship and the supportive and rich environment at JHU, will provide Dr. Cox with the skills she needs to develop into an independent researcher studying HIV/HCV coinfection immunology.